The role of Gα protein signaling in the membrane estrogen receptor-mediated signaling

Abstract

Estrogens exert rapid, extranuclear effects by their action on the plasma membrane estrogen receptors (mERs). Gα protein associated with the cell membrane is involved in many important processes regulated by estrogens. However, the Gα’s role in the mER-mediated signaling and the signaling pathways involved are poorly understood. This review aims to outline the Gα’s role in the mER-mediated signaling. Immunoblotting, immunofluorescence, co-immunoprecipitation, and RNA interference were carried out using vascular endothelial cells (ECs) and human breast carcinoma cell lines as experimental models. Electrophysiology and immunocytochemistry were carried out using guinea pigs as animal models. Recent advances suggest that the signaling of mERα through Gα is required for vascular EC migration or endothelial H₂S release, while Gα₁₃ is involved in estrogen-induced breast cancer cell invasion. Besides, the Gα_q-coupled PLC–PKC–PKA pathway is critical for the neural regulation of energy homeostasis. This review summarizes the contributions of Gα to mER-mediated signaling, including cardiovascular protection, breast cancer metastasis, neural regulation of homeostatic functions, and osteogenesis.

摘要

雌激素通过作用于质膜雌激素受体(mERs)而产生快速的核外效应。与细胞膜相关的Gα蛋白参与了雌激素调节的许多重要过程。然而, 对Gα在mER介导的信号传导中的作用以及相关的信号传导途径知之甚少。这篇综述旨在概述Gα在mER介导的信号传导中的作用。以血管内皮细胞和人乳腺癌细胞系为实验模型, 进行免疫印迹、免疫荧光、免疫共沉淀和RNA干扰。用豚鼠作为动物模型进行电生理学和免疫细胞化学。最近的进展表明, mERα通过Gα的信号传导是血管内皮细胞迁移或内皮H₂S释放所必需的, 而Gα 13参与雌激素诱导的乳腺癌细胞侵袭。此外, Gα_q偶联的PLC–PKC–PKA通路对能量稳态的神经调节至关重要。本文综述了Gα蛋白对mER介导的信号传导的贡献, 包括心血管保护、乳腺癌转移、稳态功能的神经调节和成骨过程。

Keywords:

• Estrogen
• membrane estrogen receptors
• Gα protein
• extranuclear action
• G protein

Disclosure statement

The authors of this manuscript report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No.81871137, 81471426, 81901447, 81970420, and 81900376), The Project of Principal Scientists-Guangzhou Municipal Universities ‘Yangcheng Scholars’ (1201541587), The Project of Department of Education of Guangdong Province (2015KTSCX109), National Funds of Developing Local Colleges and Universities (B16056001), Science and Technology Program of Guangzhou (No.201804010376 and 201904010289), Guangzhou 121 Talent Program, Outstanding Young Medical Talent Program in Guangdong Province and Innovation Team Project of Educational Commission of Guangdong Province of China, National Natural Science Foundation for Young Scientists of China (81800428), and the Guangdong Natural Science Foundation (No.2018A030310178, 2018A030313733, and 2018A030313657).